Process for preparing flavonoids

Abstract

A simple and easy process for preparing pharmacologically useful flavonoid compound having reductase inhibitory effect, active oxygen extinguishing effect, carcinogenesis promotion inhibitory effect, anti-inflammatory effect, and so on. Particularly, a process for preparing the compound of the formula (I): wherein, R 2 is a substituted or un-substituted phenyl group; R 7 is a hydrogen atom or a hydroxyl group; and n is an integer of 1 to 4; by bonding a sugar derivative to catechins as the starting compound selectively via O-glycoside bond and then oxidizing the 4-position of flavanoid skeleton of the obtained compound.

What is claimed is:  
     
       1. A process for preparing a compound represented by the following formula (I):                    
       wherein, R 2  is a substituted or un-substituted phenyl group; R 7  is a hydrogen atom or a hydroxyl group; and n is an integer of 1 to 4;  
       which process is characterized in that reacting a compound of the following formula (II):                    
       wherein, R 1  is a hydroxyl protecting group; R 2  and n have the same meanings mentioned above,  
       with a sugar compound of the following formula (III):                    
       wherein, R 3 , R 4  and R 5  are independently each other, a hydrogen atom or a hydroxyl protecting group; R 6  is a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and X is a halogen atom or an acyloxy group,  
       to produce a compound of following formula (IV):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       then, oxidizing of 4-position of the flavonoid skeleton of the compound of the formula (IV) obtained above to produce a compound of the following                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       and removing the hydroxyl protecting group of the compound of the formula (V) obtained above to produce the compound of the formula (I). 
     
     
       2. A process for preparing a compound represented by the following formula (I):                    
       wherein, R 2  is a substituted or un-substituted phenyl group; R 7  is a hydrogen atom or a hydroxyl group; and n is an integer of 1 to 4;  
       which process is characterized in that reacting a compound of the following formula (II):                    
       wherein, R 1  is a hydroxyl protecting group; R 2  and n have the same meanings mentioned above,  
       with a sugar compound of the following formula (III):                    
       wherein, R 3 , R 4  and R 5  are independently each other, a hydrogen atom or a hydroxyl protecting group; R 6  is a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and X is a halogen atom or an acyloxy group,  
       to produce a compound of following formula (IV):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       then, oxidizing of 4-position of the flavonoid skeleton of the compound of the formula (IV) obtained above to produce a compound of the following formula (VI):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       subsequently, further oxidizing of 4-position of the flavonoid skeleton of the compound of the formula (VI) obtained above to produce a compound of the following formula (V):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       and removing the hydroxyl protecting group of the compound of the formula (V) obtained above to produce the compound of the formula (I). 
     
     
       3. A process for preparing a compound represented by the following formula (I):                    
       wherein, R 2  is a substituted or un-substituted phenyl group; R 7  is a hydrogen atom or a hydroxyl group; and n is an integer of 1 to 4;  
       which process is characterized in that oxidizing of 4-position of the flavonoid skeleton of a compound of the following formula (IV):                    
       wherein, R 1  is a hydroxyl protecting group; R 2  is a substituted or un-substituted phenyl group; R 3 , R 4  and R 5  are independently each other, a hydrogen atom or a hydroxyl protecting group; R 6  is a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and n is an integer of 1 to 4,  
       to produce a compound of the following formula (V):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       and removing the hydroxyl protecting group of the compound of the formula (V) obtained above to produce the compound of the formula (I). 
     
     
       4. A process for preparing a compound represented by the following formula (I):                    
       wherein, R 2  is a substituted or un-substituted phenyl group; R 7  is a hydrogen atom or a hydroxyl group; and n is an integer of 1 to 4;  
       which process is characterized in that oxidizing of 4-position of the flavonoid skeleton of a compound of the following formula (IV):                    
       wherein, R 1  is a hydroxyl protecting group; R 2  is a substituted or un-substituted phenyl group; R 3 , R 4  and R 5  are independently each other, a hydrogen atom, a hydroxyl group or a hydroxyl protecting group; R 6  is a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and n is an integer of 1 to 4;  
       to produce a compound of the following formula (VI):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       subsequently, further oxidizing of 4-position of the flavonoid skeleton of the compound of the formula (VI) obtained above to produce a compound of the following formula (V):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       and removing the hydroxyl protecting group of the compound of the formula (V) obtained above to produce the compound of the formula (I). 
     
     
       5. The process according to any one of  claims 1  to  4 , wherein the compound of the formula (I) is a compound of the following formula (I-a):                    
       wherein, R 2  is a substituted or un-substituted phenyl group; R 7  is a hydrogen atom or a hydroxyl group.  
     
     
       6. The process according to any one of  claims 1  to  4 , wherein the compound of the formula (I) is a compound of the following formula (I-b):                    
     
     
       7. The process according to any one of  claims 1  to  4 , wherein the compound of the formula (I) is a compound of the following formula (I-c):                    
     
     
       8. A process for preparing a compound represented by the following formula (V):                    
       wherein, R 1  is a hydroxyl protecting group; R 2  is a substituted or un-substituted phenyl group; R 3 , R 4  and R 5  are independently each other, a hydrogen atom or a hydroxyl protecting group; R 6  is a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and n is an integer of 1 to 4,  
       which process is characterized in that oxidizing of 4-position of the flavonoid skeleton of a compound of the following formula (IV):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above.  
     
     
       9. A process for preparing a compound represented by the following formula (V):                    
       wherein, R 1  is a hydroxyl protecting group; R 2  is a substituted or un-substituted phenyl group; R 3 , R 4  and R 5  are independently each other, a hydrogen atom or a hydroxyl protecting group; R 6  is a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and n is an integer of 1 to 4,  
       which process is characterized in that oxidizing of 4-position of the flavonoid skeleton of a compound of the following formula (IV):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       to produce a compound of the following formula (VI):                    
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and n have the same meanings mentioned above,  
       and further oxidizing of 4-position of the flavonoid skeleton of the compound of the formula (VI) obtained above to produce a compound of the following formula (V).